OTHER OXYGEN METABOLISM



The range of heme functions:


Heme proteins have a broad range of functions: hemoglobin and myoglobin participate in the transport of oxygen; cytochromes of the a, b and c type undergo oxidation-reduction reactions in the electron transport chain.

Heme proteins called cytochrome P450 catalyze reactions in which oxygen is incorporated into organic molecules.


Electron transport to cyto P450





This type of reaction is not carried out directly by a single enzyme, it actually consists of a series of three:

a. a NADPH - flavoprotein dehydrogenase
b. a 2 Fe-2 S iron sulfur protein
c. the cytochrome P450 hydroxylase


Oxygen redox chemistry:

Oxygen has a negative valence except when it is combined with F. 

C-O-H   		O = -2

H-O-O-H 		O = -1

O=O- (Superoxide Anion)	O = -1/2

O=O			O =  0


The two oxygens (O2) undergoes gain a total of 4 electron during the hydroxylation reaction:

cytochrome P-450 hydroxylase
R-H + O2 + NADPH -----------> R-O-H + H2O + NADP+

2e- gained by each oxygen atom; 2e- come from NADPH, and 2e- come from the substrate (usually a methylene group).


Cytochrome redox cycle:

substrate + P-450-Fe3+ ----> P-450-Fe3+-substrate (low spin Fe)

P-450-Fe3+-substrate + Fe2S2 (1e-) ----> P-450-Fe2+-substrate (high spin Fe)

P-450-Fe2+-substrate + O2 ----> P-450-Fe2+-O2-substrate

P-450-Fe2+-O2-substrate + Fe2S2 (1e-) ----> Fe2S2 (ox.) + P-450-Fe2+-O2--substrate

P-450-Fe2+-Ov--substrate + 2 H+ ----> P-450-Fe3+ + substrate-OH + H2O






The cancer connection

Cancer-causing agents:

a. Natural constituents in foods (est.) 35%
b. Tobacco (lung and bladder) 30%
c. Sexual and reproductive history 7%
d. Occupational hazards 4%
5. Alcohol (tongue, pharynx, & esophagus) 3%
6. Food additives 1%
7. Unknown 20%

Source: American Medical Association Encyclopedia of Medicine


Cancer as a biochemical process:

a. DNA + U.V. light ----> chemically modified DNA (skin cancer)
b. DNA + O2 ----> chemically modified DNA
c. DNA + alkylating agents ----> chemically modified DNA
d. DNA + intercalating agents ----> chemically modified DNA

Modified bases or DNA sequences that are not repaired prior to the next round of DNA replication can introduce mutations into a variety of genes. Cytochrome P-450 hydroxylases contribute to this process by converting what may be relatively safe aromatic chemicals into amphipathic aromatic molecules that act as intercalating agents (see category d. above).